This proposal concerns an integrative investigation of the structural and functional characteristics of arterial resistance vessels and their involvement in hypertension. Small arteries and arterioles from the spontaneously hypertensive rat (SHR) and the normotensive Wistar Kyoto rat will be used. We are interested in answering such questions as: (1) whether the hyper-responsiveness of these vessels found in the SHR is due to altered reactivity of the smooth muscle cells and/or geometrical factors such as the wall-to-lumen ratio; (2) what adaptations occur in these vessels during the course of hypertension and the possible reasons that pressure remains elevated; (3) why therapy is effective in lowering blood pressure but does not seem to reverse the hypersensivity of the vessels to chemical agonists; (4) what changes may occur in the contractile properties of the smooth muscle cells during the course of hypertension, and what their time relationship is in regard to other adaptive cardiovascular parameters; (5) whether the cells themselves in the SHR are more responsive to the normal agonist, NE; (6) what morphological and functional alterations occur as a result of hypertensive drug therapy.